Endovascular treatment of acute ischemic stroke is now the standard of care for patients with acute ischernic stroke due to large vessel occlusion in the anterior circulation. During various endovascular treatments, a surgeon will advance clot-retrieval or clot-suction devices into the brain's vasculature to the location of the clot where the clot is either withdrawn and/or aspirated from the clot site.
As is known, when a patient experiences a significant ischemic stroke event, those portions of the brain distal to the occlusion that experience a dramatic reduction in blood supply will affect the functioning of large regions of neurons. This reduction in blood supply may cause the patient to become symptomatic, cause the death of regions of the brain and/or put regions of the brain at the risk of dying if not treated quickly. Depending on the location and size of the occlusion will result a wide range of symptoms in the patient and depending on the severity will ultimately determine how a physician may choose to intervene or not.
It is well known that time delays in effecting treatment will typically result in the death of a greater number of neurons. Table 1 shows that in the specific case of acute ischemic stroke, the pace or rate of neural circuitry loss in a typical large vessel supratentorial acute ischemic stroke can be very rapid.
TABLE 1Estimated Pace of Neural Circuitry Loss in Typical Large Vessel,Supratentorial Acute Ischemic StrokeEstimated Pace of Neural Circuitry Loss in Typical Large Vessel,Supratentorial Acute Ischemic StrokeNeuronsSynapsesMyelinatedAcceleratedLostLostFibers LostAgingPer Stroke 1.2 billion 8.3 trillion7140 km/4470 36 yrsmilesPer Hour120 billion830 billion714 km/447 miles3.6 yrsPer 1.9 million 14 billion 12 km/7.5 miles3.1 weeksMinutePer32,000230200 meters/2188.7 hoursSecondmillionyards
The numbers presented above represent an average and as understood there is a very high degree of variability based on the available blood supply to the ischemic region through collateral channels. However, as can be seen, delays in making a decision in the order of only a few minutes can have a significant impact on neural circuitry loss and ultimately patient outcome.
Moreover, a slight reduction in blood supply can tip the balance and dramatically further increase the rate of cell death.
In diagnosing and treating ischemic stroke, it is important for the physician to know where the vessel occlusion is, how big the occlusion is, where any dead brain tissue (termed “core”) is and, how big and where is the brain tissue that may have been affected by the ischernic event but that may potentially be saved (termed “penumbra”).
More specifically, the penumbra is tissue around the ischemic event that can potentially stay alive for a number of hours after the event by the perfusion of this tissue by collateral arteries. That is, the collateral arteries may provide sufficient oxygen, nutrients and/or flushing to the penumbra tissue to prevent this tissue from dying for a period of time.
Anatomical Variables
There are many anatomical considerations that can affect the severity and ultimately treatment of ischemic stroke. Importantly, as above, while a blood clot may severely affect blood flow to the ischemic area, some blood flow may get to the ischemic area if collateral arteries are functioning to at least partially perfuse the affected area.
The most common large vessel occlusion that is treated by endovascular techniques is the M1 segment of the middle cerebral artery (MCA). When a patient has an M1 occlusion, the territory supplied by the M1 receives a dramatic reduction in blood supply. As a consequence distal neurons don't function well and the patient becomes symptomatic. Preferably, there is some blood flow that manages to get to the ischemic territory through collaterals which may decrease the rate of neuronal death. Generally, in this case, the collaterals are the connections between the distal most branches of the anterior cerebral artery and the middle cerebral artery (or the posterior cerebral artery and the middle cerebral artery).
In different patients, collaterals are highly variable and there are a number of factors at play which are not fully understood. Some of these factors are genetic in nature but conditions such as hypertension and diabetes (and other poorly understood factors) may also reduce the efficacy of collaterals in different patients.
Importantly, regardless of the patient's anatomy, the maintenance of collateral blood flow is critical to keep the brain alive until the time the occluded vessel can be recanalized and blood flow re-established.
It is not well understood what keeps collaterals open but, amongst various factors, the pressure head in the vessel supplying the collaterals is considered important. In addition, systemic pressure and/or chemical factors that may be produced locally by the ischemic brain may also contribute.
In the case of an M1 occlusion, the collaterals between the anterior carotid artery (ACA) and the middle carotid artery (MCA) are likely kept open by the pressure in the ACA.
Other anatomical factors that may affect blood flow during a stroke including the effect of blood flow through the Circle of Willis (COW). FIG. 1 is a schematic diagram showing the major arteries within the cerebral vasculature and FIG. 2 is a schematic diagram showing variations in COW blood flow within the population which can affect collateral blood flow in the event of a stroke.
Importantly, the arrangement of the brain's arteries into the Circle of Willis creates redundancies in the cerebral circulation such that if one part of the circle becomes blocked or narrowed (stenosed) or one of the arteries supplying the circle is blocked or narrowed, blood flow from the other blood vessels can often preserve the cerebral perfusion well enough to avoid the symptoms of ischemia through collaterals. As shown in FIG. 2, there is significant variation between individuals' COW anatomy (both inherent and age related factors) such that an individual's COW anatomy can significantly affect collateral blood flow in the event of a stroke.
In particular, important connections at the COW include:                a. Anterior communication artery. This artery is the connection between the two anterior cerebral arteries (FIG. 1). The functionality of this part of the COW is dependent on the presence of good sized A1 segments of the anterior cerebral arteries as well.        b. Posterior communicating artery: This artery is a communication between the internal carotid artery (ICA) and the ipsilateral posterior cerebral artery (PCA). For good functionality of this part of the COW there also needs to be a good sized P1 segment of the PCA.        
In a patient who has occlusion of the terminal ICA and M1 segment of the MCA, the only way for the anterior part of the MCA territory to stay alive is for the blood to come from the other ICA, go across the anterior communicating artery and finally through the ACA-MCA collaterals to supply the anterior part of the MCA territory. In such a patient if there is an insufficient COW, the brain tissue dies very quickly before any treatment can be administered.
Similarly in a patient who had a fetal PCA (PCA comes off the ICA with a hypoplastic or small P1 segment (FIG. 2), in the presence of a terminal ICA and M1 clot the posterior part of the MCA territory is unable to survive due to lack of filling of the MCA-PCA collaterals.
In patients with M1 occlusion, if the ICA is widely patent (there is no significant stenosis) and there is a good ipsilateral A1 segment, the collaterals are not dependent on the COW. However in such a situation, if there is a compromise in the flow through the ICA, the presence of a patent COW can compensate for the reduced pressure head in the distal ACA.
In most situations, the COW has potential connections that may have very little flow through it.
For example, it is quite common to have a hypoplastic A1 segment of the anterior cerebral artery in which case the distal ACA is primarily supplied through the anterior communicating artery from the contralateral side (FIG. 2B).
Other situations such as person's neck position can also influence flow through the COW.
Methodologies of Endovascular Thrombectomy and Effect on Collateral Flow
Broadly, there are two main techniques used for recanalizing an occluded vessel intracranially. The two of them can be used in conjunction with each other and include:                a. Stent Retriever—A stent retriever is a device comprising a compressed wire framework that is advanced to the clot within a catheter, whereupon reaching the clot, the stent retriever is unsheathed from the catheter allowing it to expand within the clot whereby the clot becomes entangled within the wire frame of the device, allowing the physician to withdraw the device with the clot entangled therein.        b. Aspiration—With this technique, a large bore catheter that is very flexible in negotiated by the physician to the level of the thrombus that is occluding the vessel. Once the catheter is close to the clot, negative (retrograde) pressure is applied either through a pump or manually such that the clot is aspirated through the catheter by the strong negative pressure.        
Based on clinical experience and computational flow dynamics studies, it is generally understood that the presence of large bore catheters significantly affects collateral flow and pressure head in patients with ‘relatively isolated’ circulation and presence of M1 occlusion.
More specifically, the degree of flow and/or pressure reduction is influenced by:                a. ratio of a catheter diameter vs. parent vessel diameter.        b. size of alternative pathways (e.g. small Acom).        c. how distal the catheter is and its tortuosity within the vessels (e.g. a balloon guide catheter in the proximal ICA may be less obstructive than a DAC (distal access catheter) within the intracranial ICA). That is, the action of pushing a catheter through a small vessel having complex curvatures has an affect particularly as the catheter progresses further into the brain and the relative difference in size between the catheter and inner diameter of the vessel it is advancing through becomes smaller.        d. Other factors such as the systemic Blood Pressure may also contribute.        
In addition, it also generally understood that applying suction (retrograde flow) further reduces the flow through collaterals as the negative pressure has the effect of reducing blood pressure in areas immediately surrounding where the negative pressure is being applied.
Accordingly, there has been a need for systems and methods that improve the flow of blood through collaterals that may be diminished as a result of endovascular treatment. In particular, there has been a need for systems and methods that maintain or enhance antegrade flow through the vasculature through which catheters may be progressing and/or maintaining antegrade flow at desired perfusion pressures while retrograde flow is active during clot removal.
Additionally, there has been a need for systems that can not only maintain the perfusion pressure but also improve nutritional delivery (oxygen, glucose etc) to the ischemic tissue. In addition there has been a need for systems that can improve flow by altering the physical characteristics of the blood (e.g. reduce viscosity).